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US20040147724A1 - Nuclear hormone receptor ligand binding domain - Google Patents

Nuclear hormone receptor ligand binding domain Download PDF

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Publication number
US20040147724A1
US20040147724A1 US10/469,780 US46978004A US2004147724A1 US 20040147724 A1 US20040147724 A1 US 20040147724A1 US 46978004 A US46978004 A US 46978004A US 2004147724 A1 US2004147724 A1 US 2004147724A1
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Prior art keywords
polypeptide
nucleic acid
disease
acid molecule
ligand binding
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US10/469,780
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Inventor
Richard Fagan
Christopher Phelps
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Inpharmatica Ltd
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Inpharmatica Ltd
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Assigned to INPHARMATICA LIMITED reassignment INPHARMATICA LIMITED ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: FAGEN, RICHARD JOSEPH, PHELPS, CHRISTOPHER BENJAMIN
Publication of US20040147724A1 publication Critical patent/US20040147724A1/en
Abandoned legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/72—Receptors; Cell surface antigens; Cell surface determinants for hormones
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Definitions

  • Modifications can occur anywhere in a polypeptide, including the peptide backbone, the amino acid side-chains and the amino or carboxyl termini.
  • blockage of the amino or carboxyl terminus in a polypeptide, or both, by a covalent modification is common in naturally-occurring and synthetic polypeptides and such modifications may be present in polypeptides of the present invention.
  • the nucleic acid molecules of the invention also include antisense molecules that are partially complementary to nucleic acid molecules encoding polypeptides of the present invention and that therefore hybridize to the encoding nucleic acid molecules (hybridization).
  • antisense molecules such as oligonucleotides, can be designed to recognise, specifically bind to and prevent transcription of a target nucleic acid encoding a polypeptide of the invention, as will be known by those of ordinary skill in the art (see, for example, Cohen, J. S., Trends in Pharm. Sci., 10, 435 (1989), Okano, J. Neurochem. 56, 560 (1991); O'Connor, J. Neurochem 56, 560 (1991); Lee et al., Nucleic Acids Res 6, 3073 (1979); Cooney et al., Science 241, 456 (1988); Dervan et al., Science 251, 1360 (1991).
  • Another technique for drug screening which may be used provides for high throughput screening of compounds having suitable binding affinity to the polypeptide of interest (see International patent application WO84/03564).
  • This method large numbers of different small test compounds are synthesised on a solid substrate, which may then be reacted with the polypeptide of the invention and washed.
  • One way of immobilising the polypeptide is to use non-neutralising antibodies. Bound polypeptide may then be detected using methods that are well known in the art. Purified polypeptide can also be coated directly onto plates for use in the aforementioned drug screening techniques.
  • the polypeptide of the invention may be used to identify membrane-bound or soluble receptors, through standard receptor binding techniques that are known in the art, such as ligand binding and crosslinking assays in which the polypeptide is labelled with a radioactive isotope, is chemically modified, or is fused to a peptide sequence that facilitates its detection or purification, and incubated with a source of the putative receptor (for example, a composition of cells, cell membranes, cell supernatants, tissue extracts, or bodily fluids).
  • a source of the putative receptor for example, a composition of cells, cell membranes, cell supernatants, tissue extracts, or bodily fluids.
  • the efficacy of binding may be measured using biophysical techniques such as surface plasmon resonance and spectroscopy.
  • compositions will generally be accomplished by injection, subcutaneously, intraperitoneally, intravenously or intramuscularly, or delivered to the interstitial space of a tissue.
  • the compositions can also be administered into a lesion. Dosage treatment may be a single dose schedule or a multiple dose schedule.
  • Deletions and insertions can be detected by a change in the size of the amplified product in comparison to the normal genotype.
  • Point mutations can be identified by hybridizing amplified DNA to labelled RNA of the invention or alternatively, labelled antisense DNA sequences of the invention. Perfectly-matched sequences can be distinguished from mismatched duplexes by RNase digestion or by assessing differences in melting temperatures.

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US10/469,780 2001-03-05 2002-03-05 Nuclear hormone receptor ligand binding domain Abandoned US20040147724A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB0105401.4 2001-03-05
GBGB0105401.4A GB0105401D0 (en) 2001-03-05 2001-03-05 Novel proteins
PCT/GB2002/000941 WO2002070558A2 (fr) 2001-03-05 2002-03-05 Domaine de liaison du ligand du recepteur hormonal nucleaire

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US20040147724A1 true US20040147724A1 (en) 2004-07-29

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US10/469,864 Abandoned US20040170999A1 (en) 2001-03-05 2002-03-05 Nuclear hormone receptor ligand binding domain
US10/469,862 Abandoned US20040171804A1 (en) 2001-03-05 2002-03-05 Nuclear hormone receptor ligand binding domain
US10/469,780 Abandoned US20040147724A1 (en) 2001-03-05 2002-03-05 Nuclear hormone receptor ligand binding domain
US10/469,858 Abandoned US20040132038A1 (en) 2001-03-05 2002-03-05 Nuclear hormone receptor ligand binding domain

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US10/469,862 Abandoned US20040171804A1 (en) 2001-03-05 2002-03-05 Nuclear hormone receptor ligand binding domain

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US (4) US20040170999A1 (fr)
EP (4) EP1373316A2 (fr)
JP (4) JP2005500014A (fr)
AU (3) AU2002234782A1 (fr)
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WO2002070561A2 (fr) 2002-09-12
EP1404714A2 (fr) 2004-04-07
AU2002234783A1 (en) 2002-09-19
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EP1373316A2 (fr) 2004-01-02
WO2002070562A3 (fr) 2003-12-31
US20040171804A1 (en) 2004-09-02
EP1366079A2 (fr) 2003-12-03
CA2439197A1 (fr) 2002-09-12
EP1370586A2 (fr) 2003-12-17
CA2439200A1 (fr) 2002-09-12
WO2002070558A2 (fr) 2002-09-12
JP2005500820A (ja) 2005-01-13
JP2005500011A (ja) 2005-01-06
JP2005500014A (ja) 2005-01-06
AU2002234781A1 (en) 2002-09-19
WO2002070562A2 (fr) 2002-09-12
CA2439203A1 (fr) 2002-09-12
US20040132038A1 (en) 2004-07-08
WO2002070558A3 (fr) 2002-12-19
CA2439195A1 (fr) 2002-09-12
GB0105401D0 (en) 2001-04-18
US20040170999A1 (en) 2004-09-02
WO2002070560A2 (fr) 2002-09-12
WO2002070560A3 (fr) 2002-12-19
AU2002234782A1 (en) 2002-09-19
JP2005500013A (ja) 2005-01-06

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